Studies from our laboratory have demonstrated that the rate of collagen synthesis significantly increases after 60 days of feeding a 2% cholesterol diet to rabbits. This change in collagen synthesis is accompanied by an increase in the rate of aortic cholesterol accumulation. The present experiments are designed to investigate the specificity of the increase in collagen synthesis. Collagen and noncollagen synthetic rates will be estimated following in vitro incorporation of C14-proline in rabbit aorta, lung and liver. Studies of changes in cholesterol biochemistry will also be investigated. Serum lipoprotein patterns, aortic permeability, aortic cholesterol esterase activity and aortic cholesterol esterification activity will be determined after 30, 60 and 90 days of cholesterol feeding. These experiments will help to elucidate the relationship between increased collagen synthesis and increased cholesterol accumulation. The hypothesis to be tested is that, in experimental atherosclerosis, the rate of cholesterol influx is affected by changes in connective tissue metabolism.